Mark Richter

Structure and dynamics of the ATP synthase and other molecular machines.

Richter Research Synopsis:

ATP synthase Structure and Function

The F1FO-ATP synthase is a tiny molecular rotary motor driven by binding and hydrolysis of ATP in one direction and by trans-membrane proton flux in the other direction. This complex multi-subunit protein generates sufficient torque to propel large (1-2 micrometers) actin filaments through solution with a remarkably high energy conversion efficiency. The photosynthetic ATP synthase of higher plants has several unique properties that separate it from its mitochondrial and bacterial counterparts and that offer unique inroads to examine the mechanism of energy coupling. One such property is the presence of a special regulatory domain in the γ subunit of higher plant species which, via the reversible oxidation/reduction of an intrinsic dithiol that governs an interaction with the inhibitory ε subunit, provides a molecular "switch" mechanism that tightly controls the catalytic activity of the enzyme. The principle goal of the proposed research is to identify the productive binding interactions between the γ and ε subunits, and between these two subunits and the other F1 subunits, that are involved in the molecular "switch" mechanism. The information to be gained from this work is likely to prove seminal in understanding natural processes that have evolved to gate the motor, in identifying the mechanism of elastic coupling between the FO and F1 segments, and in designing gated nanodevices for future industrial and biomedical applications. Ongoing projects involve: protein engineering, folding and ATPase complex assembly; NMR and crystallization studies of subunit structure; single molecule enzyme analysis using atomic force microscopy, fluorescence and dark-field microscopy; and surface patterning for on-chip fabrication of nanodevices to address industrial and biomedical needs.